Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Consenting and eligible patients will receive adaptive short course radiation therapy (SCRT) (25 Gy at in 5 fractions), followed by standard of care total neoadjuvant chemotherapy followed by standard of care gastrectomy or esophagogastrectomy. The recommended SOC chemotherapy options are CAPOX, FOLFOX, or FLOT, but any SOC total neoadjuvant chemotherapy may be given at the discretion of the treating medical oncologist after consultation with the study chair. Patients who are not able to complete their full total neoadjuvant therapy regimen prior to surgery may complete chemotherapy postoperatively at the discretion of the treating physician.

Radiation must be livered with adaptive planning and MR gating or CBCT breath hold treatment.

Adaptive short course radiation therapy

The recommendations are CAPOX, FOLFOX, or FLT.

Standard of care chemotherapy regimen

Hyun Kim, M.D.

Haeseong Park, M.D., MPH

Ryan Fields, M.D.

Katrina Pedersen, M.D.

Pamela Samson, M.D.

Carl DeSelm, M.D., Ph.D.

Kian-Huat Lim, M.D., Ph.D.

Rama Suresh, M.D.

Benjamin Tan, M.D.

Patrick Grierson, M.D.

Dominic Sanford, M.D.

Natasha Leigh, M.D.

Roheena Panni, M.D., Ph.D.

Allen Mo, M.D., Ph.D.

Gastric cancer is a global health issue as the world's fifth most common malignancy and third leading cause of cancer mortality, respectively. Preoperative radiation therapy may improve overall survival (OS) but is seldom used. There is precedent for preoperative chemoradiation, as it is the standard of care for esophageal and gastroesophageal junction tumors. However, reluctance of physicians to prescribe preoperative radiation therapy in gastric cancer may be due to the large treatment fields necessary to account for stomach motion. Adaptive radiation therapy may permit decreased field sizes and more accurate dose delivery. In traditional CT based radiation delivery the same radiation plan is delivered each day without assessment of inter-fraction or intra-fraction motion. Adaptive radiation therapy permits the physician to contour the unique anatomy daily to generate a new plan to account for day to day organ motion. Real-time MR imaging is also used during the treatment so that radiation is only delivered when the tumor is within the pre-specified target area. Thus, adaptive radiation therapy may overcome traditional barriers of radiation delivery in gastric cancer and improve oncologic outcomes.

Pre-operative Adaptive Short Court Radiation Therapy in Gastric Cancer

Pre-operative Adaptive Short Course Radiation Therapy in Gastric Cancer

Individual participant data that underlie the results reported in the journal publication, after deidentification (text, tables, figures, and appendices)

Local control from the time of gastrectomy

-Overall survival from registration on trial

-Disease free means no locoregional and distant recurrence

Viewray Inc.

Washington University School of Medicine

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Pembrolizumab

Fluorouracil

Epirubicin

Oxaliplatin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

All study subjects will receive standard of care chemotherapy regimen for 3 cycles prior to and 3 cycles following surgery in combination with Pembrolizumab with an additional cycle of Pembrolizumab (4 total) in the pre-operative period. Additionally subjects will complete 12 months of maintenance Pembrolizumab (14 additional doses to complete 17 post-operative cycles) following completion of post-operative chemotherapy.

Standard of care combination chemotherapy regimen has a 21-day cycle.

Pembrolizumab dosed IV at 200mg every 21 days per cycle.

Standard regimen containing at least a platinum and Fluorouracil (5-FU) agent (per National Comprehensive Cancer Network guidelines) - such as Doublet or Triplet chemotherapy with capecitabine, oxaliplatin, and epirubicin (optional) (21 day cycle). Epirubicin can be excluded at the discretion of the treating physician.

Example:

Oxaliplatin dosed IV at 130 mg/m2 every 21 days per cycle. Capecitabine dosed orally at 625mg/m2 twice a day daily.

Gulam Manji, MD, PhD

This is a non-randomized, multi-site, open-label trial of pembrolizumab and chemotherapy in subjects with gastric or gastroesophageal (GE) junction adenocarcinoma. The purpose of this study is to determine and evaluate the efficacy of combination therapy with immune checkpoint blockade and chemotherapy used in the perioperative period in eradicating micrometastatic disease; and to compare paired tissue and serum samples (pre-treatment and post-treatment) from individually treated patients to explore the immune effects of combination therapy and predictors of response.

Gastric cancer is one of the most common cancers worldwide. Surgical resection is the primary treatment for gastric cancer but most patients present with locally advanced disease and recurrence is common after surgery. Many patients (35%) will have early recurrence within 6-9 months of surgery indicating the need for more aggressive upfront therapy in these subjects. In addition, the majority of patients will ultimately have recurrence and 5 year survival rates are 35-40% despite aggressive therapy.

The ability to combine immunotherapy with pembrolizumab gives the potential to increase therapeutic options while continuing standard of care chemotherapy. The particular use of maintenance therapy may delay or eliminate the growth of residual micrometastatic disease and lead to durable disease control. Additionally, this study provides the foundation for substantial correlative work to define tumor and patient characteristics that may predict for response to pembrolizumab in gastric cancer.

The initial primary outcome of Disease Free Survival (DFS) was changed to pathologic complete response rate (pCR) on November 24, 2020, at which time no formal data analysis had been preformed.

Perioperative Chemo and Pembrolizumab in Gastric Cancer

A Phase II Study of Chemotherapy and Immune Checkpoint Blockade With Pembrolizumab in the Perioperative and Maintenance Treatment of Locoregional Gastric or GE Junction Adenocarcinoma.

Number of subjects with absence of viable tumor on surgical resection specimen as determined by local pathology review.

OS defined as the time from Cyle 1 Day 1 treatment administration to death due to any cause. The 24 month overall survival probability was estimated using the Kaplan-Meier method.

DFS defined as time from Cycle 1 Day 1 treatment administration to the first documented event of disease progression, disease recurrence following surgery (preferably biopsy proven), or death whichever occurs first. The 24 month DFS probability was estimated using the Kaplan-Meier method.

Number of subjects with initial RECIST 1.1 measurable disease who have complete response (CR) or partial response (PR) at any time (ORR= CR + PR). CR defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Merck Sharp & Dohme LLC

Gulam Manji

Professor of Medicine

Systematic assessment of adverse events: Routine review of and for adverse events at each scheduled visit through investigator assessment and laboratory testing. 36 participants enrolled in the study, one participant withdrew consent, therefore 35 were included in adverse events assessment.

All study subjects will receive standard of care chemotherapy regimen for 3 cycles prior to and 3 cycles following surgery in combination with Pembrolizumab with an additional cycle of Pembrolizumab (4 total) in the pre-operative period. Additionally subjects will complete 12 months of maintenance Pembrolizumab (14 additional doses to complete 17 post-operative cycles) following completion of post-operative chemotherapy.

Standard of care combination chemotherapy regimen has a 21-day cycle.

Pembrolizumab: Pembrolizumab dosed IV at 200mg every 21 days per cycle.

Standard of care chemotherapy regimen: Standard regimen containing at least a platinum and Fluorouracil (5-FU) agent (per National Comprehensive Cancer Network guidelines) - such as Doublet or Triplet chemotherapy with capecitabine, oxaliplatin, and epirubicin (optional) (21 day cycle). Epirubicin can be excluded at the discretion of the treating physician.

Example:

Oxaliplatin dosed IV at 130 mg/m2 every 21 days per cycle. Capecitabine dosed orally at 625mg/m2 twice a day daily.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pre-operative Adaptive Short Court Radiation Therapy in Gastric Cancer	NCT04162665	Gastric Adenoca...	Adaptive short ... Standard of car...	19 Years -	Washington University School of Medicine
Perioperative Chemo and Pembrolizumab in Gastric Cancer	NCT02918162	Gastric Cancer Adenocarcinoma ...	Pembrolizumab Standard of car...	18 Years -	Columbia University

Spots Global Cancer Trial Database for standard of care chemotherapy regimen